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Abstract

Two studies recently reported around 10% of EGFR activating mutations in triple negative breast cancers from Asian patients. However,
we did not find any EGFR activating mutation in a series of 229 breast tumor samples
from European patients. Like in lung cancer, the EGFR mutation profiles seem to be related to the ethnical origin of patients. This is an
important point that should be considered when developing anti-EGFR therapies.

Keywords:

Commentary

We have read with great interest the study on Epidermal Growth Factor Receptor (EGFR)
mutations in breast carcinoma by Ning Lv et al published in Diagnostic Pathology [1]. Since in lung cancer the choice of anti-EGFR therapy is based on the presence of
EGFR activating mutations, and due to the importance to the EGFR pathway in breast cancer,
it is crucial to evaluate the presence of these mutations in the different subtypes
of breast cancer. The authors reported that, in their series of 139 breast cancers,
two (1.4%) tumors harbored activating EGFR mutations in exon 19 and 21 of this gene. One tumor was classified as estrogen receptor
(ER) (1/105, 0.8%) positive and the other was a triple negative (TN) tumor (1/10,
10%). Similarly, in a recent study on 70 TN breast cancers, which were previously
described to often present an EGFR addiction, Teng et al. found 8 (11.4%) activating
EGFR mutations in exon 19 and 21 [2]. Both works reported findings that were obtained using tumor samples from Asian patients.
We recently analyzed a series of 229 TN tumor samples from European patients with
primary breast cancer and found that none had activating EGFR mutations [3]. In previous reports concerning smaller series of Caucasians patients, no EGFR activating mutation was found whatever the subtype of breast cancer studied [4-6]. Similarly, in a cohort of 58 Japanese patients, Toyama et al failed to find exon
19 and 21 EGFR mutations [7]. These results underline geographic differences in the presence of EGFR activating mutations as it was already described for non-small cell lung cancer [8]. This mutational event, which appears to be mostly limited to Chinese patients with
TN breast cancer, could be related to ethnic or environmental factors. However, the
question of the origin of the geographical variations in the occurrence of EGFR mutations in lung and breast cancers is unresolved.

Interestingly, a case of breast metastasis from a primary lung cancer that was confirmed
by the detection of the same EGFR mutation has been recently reported [9]. This observation confirms that the presence of this mutation is not an obstacle
to metastasization/tumor cell growth in the breast microenvironment. Inversely, we
should not forget that some breast cancer characteristics, like ER expression and
HER2 over-expression, have been also described in lung cancers [10,11]. Lung and breast cancer subtypes seem to share some biomarkers and thus could respond
to the same therapies.

At the time of personalized medicine in oncology, more than ever, molecular patterns
break the limits of classifying tumors according to their localization. Mutation profiles
have to be analyzed in sub-groups of specific populations. This is a new and promising
challenge for the design of clinical trials involving targeted therapies.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

PJL has been involved in drafting the manuscript. WJ has been involved in the critical
revision of the manuscript intellectual content. All authors read and approved the
final manuscript.